Unprecedented synthesis of a 14-membered hexaazamacrocycle

• Published in: Beilstein journal of organic chemistry Vol. 19; no. 1; pp. 1728 - 1740
• Main Authors: Fesenko, Anastasia A, Shutalev, Anatoly D
• Format: Journal Article
• Language: English
• Published: Frankfurt am Main Beilstein-Institut zur Föerderung der Chemischen Wissenschaften 2023; Beilstein-Institut
• Subjects: amidrazones; Carbon; Dimerization; hexaazamacrocycles; Hydrazine; Hydrocarbons; Pyrazoles; pyrazolo[3,4-d]pyrimidines; ring contraction; self-assembly
• ISSN: 1860-5397; 2195-951X; 1860-5397
• DOI: 10.3762/bjoc.19.126

The transformation of 3-[(ethoxymethylene)amino]-1-methyl-1 H -pyrazole-4-carbonitrile into the 14-membered macrocycle, 2,10-dimethyl-2,8,10,16-tetrahydrodipyrazolo[3,4- e :3',4'- l ][1,2,4,8,9,11]hexaazacyclotetradecine-4,12-diamine, by the reaction with excess hydrazine under various conditions was studied in detail. The reaction proceeded through the initial formation of 4-imino-2-methyl-2,4-dihydro-5 H -pyrazolo[3,4- d ]pyrimidin-5-amine followed by dimerization to give the final macrocycle. A convenient synthesis of the latter starting from 4-imino-2-methyl-2,4-dihydro-5 H -pyrazolo[3,4- d ]pyrimidin-5-amine was developed. A plausible pathway for the macrocycle self-assembly is discussed. Some features of the structure and reactivity of the obtained macrocycle are outlined.